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  • Tom Guttuso

"Promise of Lithium" is already out of date!

Well, that was fast. The official book launch isn't until 1/31/23 and it's already in need of an update in terms of recently approved treatments for Alzheimer's disease (AD). So, here it is:

On January 6, 2023, the Food and Drug Administration (FDA) approved the drug lecanemab for treating patients with very early AD. This was based on a study showing this drug to slow cognitive decline by 27% compared to patients receiving placebo in addition to its ability to clear a sticky protein called beta-amyloid from the brain. The drug was approved through a special "accelerated approval" pathway that the FDA established to allow patients quick access to new therapies that addressed diseases with an unmet need such as AD. It remains to be determined if the FDA will grant "full approval" to lecanemab and if major insurance companies including Medicare will cover the $26,500 annual price tag.

In "The Promise of Lithium", the highly controversial FDA approval on June 7, 2021 of the drug aducanumab for treating AD was reviewed. Like lecanemab, aducanumab also cleared beta-amyloid from the brain; however, only one of the two aducanumab studies showed that it improved AD patient's symptoms. Because of the inconsistencies in these studies, most experts do not believe that the evidence sufficiently supports FDA-approval of aducanumab and several private insurance companies as well as Medicare have refused to cover the cost of aducanumab.

In addition, both lecanumab and aducanumab can cause brain swelling and brain bleeding. These side effects are usually mild and don't cause any new symptoms in patients; however, potential long term effects of these brain changes caused by lecanemab and aducanumab are still unknown.

In summary, there are now two FDA-approved "disease-modifying" treatments for patients in the very early stages of AD that may slow down the progression of AD symptoms; however, neither has received full FDA approval and neither has received Medicare coverage. Because the vast majority of AD patients are over 65 years old, Medicare coverage will be essential for the wide-spread use of these very expensive therapies. If Medicare does eventually approve coverage for one or both of these drugs, it likely will be restricted only for recently diagnosed AD patients who are still in the earliest stages of the disease.

Although it is exciting for AD patients to finally see some positive news after years of failed clinical trials, there clearly is much more that needs to be done to improve AD patients' lives. First of all, the 27% reduced rate of cognitive decline in early AD shown for lecanemab is a fairly small treatment effect size. Because of this small magnitude of benefit, it is unclear if lecanemab can provide long-term, meaningful benefit for AD patients. Also, it is unclear how problematic the brain swelling and brain bleeding side effects from both lecanemab and aducanumab will be with long-term treatment. Finally, these findings only apply to early AD patients. It sure would be nice to have something to offer AD patients who are not in the earliest stages to help slow down their disease progression.

Fortunately, the LATTICE trial that is discussed in detail in "The Promise of Lithium" is underway at the University of Pittsburgh with results expected in late 2024. The LATTICE trial seeks to determine if low-dose lithium therapy can slow cognitive decline and brain changes in early AD patients. Previous studies with low-dose lithium in both early and more mid-stage AD have shown positive results with much larger treatment effect sizes than that seen with lecanemab. These studies were also reviewed in detail in "The Promise of Lithium". Of course, further research is needed but it is very encouraging to see a major lithium study like LATTICE underway.

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